[Role of inhibition of transcription factor forkhead box M1 expression by RNA interference in the proliferation and invasiveness of non-small cell lung cancer cells]

Abstract

Objective: To investigate the change of proliferation and invasiveness of non-small cell lung cancer (NSCLC) cell lines SPC-A-1, A549 and LTEP-a-2 with forkhead box M1 (FoxM1) expression deficiency.

Methods: A siRNA targeting FoxM1 was designed to deplete the FoxM1 expression of these cell lines and an unrelated siRNA used as control. Real-time RT-PCR and Western blotting were used to examine the FoxM1 expression in mRNA and protein level respectively. Colony assay, wound healing assay and transwell chamber assay were employed to evaluate the colony formation ability and invasiveness of FoxM1 deficient cells.

Results: The designed siRNA could efficiently deplete FoxM1 expression by 83.9%, 83.6% and 88.6% in SPC-A-1, A549 and LTEP-a-2 cell lines respectively. Real-time RT-PCR and Western blot test showed that the FoxM1 protein was also depleted. The colony formation numbers (136.0 +/- 15.5, 87.0 +/- 2.6 and 121.7 +/- 9.4 respectively) and invasion cell numbers (19.2 +/- 2.5, 4.2 +/- 0.8 and 6.2 +/- 1.8 respectively) of FoxM1 deficient SPC-A-1, A549 and LTEP-a-2 cell lines were significantly fewer than those of the unrelated-siRNA transfected group (colony formation numbers were 222.3 +/- 20.5, 164.7 +/- 14.1 and 260.7 +/- 13.5 respectively, and invasive cell numbers were 81.4 +/- 6.2, 39.2 +/- 4.6 and 35.6 +/- 3.0 respectively, all P < 0.01). The cell migration rate of siFoxM1 deficient SPC-A-1 (52.6% +/- 7.8%) was significantly lower than that of the unrelated-siRNA transfected group (85.3% +/- 18.6%, P < 0.01).

Conclusions: The proliferation and invasiveness of several NSCLC cell lines were significantly inhibited after the FoxM1 gene expression was depleted. It suggests that inhibiting the FoxM1 expression might be a promising way for lung cancer therapy.